2024-03-28T09:42:33Z
https://niigata-u.repo.nii.ac.jp/oai
oai:niigata-u.repo.nii.ac.jp:00033924
2022-12-15T04:04:11Z
453:455
471:561:562
G3BP1はp62とUSP10によるユビキチン化蛋白質の凝集体形成を抑制する
G3BP1 inhibits ubiquitinated protein aggregations induced by p62 and USP10
Anisimov, Sergei
177891
新潟大学
博士(医学)
The aberrant accumulation of ubiquitinated protein aggregates in cells plays a critical role in the pathogenesis of several degenerative diseases, including Parkinson disease (PD) and cystic fibrosis (CF). In this study, we found that Ras GTPase-activating protein-binding protein 1 (G3BP1) inhibits ubiquitinated protein aggregations induced by p62 and USP10 in cultured cells. p62 is a ubiquitin receptor, and p62 and its binding partner USP10 have been shown to augment ubiquitinated protein aggregation. G3BP1 interacted with p62 and USP10 and inhibited p62/USP10-induced protein aggregation. The G3BP1 inhibition of protein aggregations targeted two aggregation-prone proteins, α-synuclein and CFTR-∆F508, which are causative factors of PD and CF, respectively. G3BP1 depletion increased the amounts of ubiquitinated α-synuclein and CFTR-∆F508 protein. A proteasome reporter indicated that G3BP1 depletion inhibits the proteasome activity. We herein present evidence that G3BP1, p62 and USP10 together control ubiquitinated protein toxicity by controlling both ubiquitination and aggregation. Taken together, these results suggest that G3BP1, p62 and USP10 could be therapeutic targets for ubiquitinated protein aggregation disorders, including PD and CF.
Scientific Reports. 2019, 9(1), 12896
新大院博(医)甲第901号
thesis
2019-09-20
application/pdf
application/pdf
13101甲第4641号
https://niigata-u.repo.nii.ac.jp/record/33924/files/r1nmk901.pdf
https://niigata-u.repo.nii.ac.jp/record/33924/files/r1nmk901_a.pdf
eng
info:doi/10.1038/s41598-019-46237-1